As part of a long term goal to understand the regulation of cell behavior by the extracellular matrix, this research focuses on heparan sulfate proteoglycans at the cell surface. These proteoglycans are at the surfaces of all adherent cells and undergo changes in expression and glycosylation during development, neoplasia, local invasion and metastasis. One integral membrane proteoglycan, syndecan, binds a diverse set of ligands, links the extracellular matrix to the cytoskeleton, varies in its location at the cell surface and in the number and size of its glycosaminoglycan chains depending on cell type and organization, and has a unique core protein sequence which bears heparan sulfate chains containing heparin-like domains. Recent results lead to the working hypothesis that syndecan and related molecules appear to have multiple functions because they can bind a variety of biological effector molecules and can act in partnership or combination with other cell surface receptors to alter cellular behavior. The specific aims of this research are to: (i) define the interaction of various extracellular ligands with syndecan by assessing their binding to the structurally polymorphic forms of syndecan, (ii) test whether syndecan acts in combination with other receptors by comparing the responses of syndecan-deficient and syndecan-replete cells to various ligands, (iii) demonstrate the function of various core protein domains of syndecan by expressing native and mutant syndecans on cells that do not express cell surface syndecan, and (iv) determine whether syndecan is a member of a gene family by preparing antibody and cDNA probes based on syndecan sequences that are conserved between species, and by purifying and identifying candidate syndecan-like core proteins.